Collagen VI is widely distributed throughout extracellular matrices (ECMs) in various tissues. In skeletal muscle, collagen VI is particularly concentrated in and adjacent to basement membranes of myofibers. Ullrich congenital muscular dystrophy (UCMD) is caused by mutations in either COL6A1, COL6A2 or COL6A3 gene, thereby leading to collagen VI deficiency in the ECM. It is known to occur through either recessive or dominant genetic mechanism, the latter most typically by de novo mutations. UCMD is well defined by the clinicopathological hallmarks including distal hyperlaxity, proximal joint contractures, protruding calcanei, scoliosis and respiratory insufficiency. Recent reports have depicted the robust natural history of UCMD; that is, loss of ambulation by early teenage years, rapid decline in respiratory function by 10 years of age and early-onset, rapidly progressive scoliosis. Muscle pathology is characterised by prominent interstitial fibrosis disproportionate to the relative paucity of necrotic and regenerating fibres. To date, treatment for patients is supportive for symptoms such as joint contractures, respiratory failure and scoliosis. There have been clinical trials based on the theory of mitochondrion-mediated myofiber apoptosis or impaired autophagy. Furthermore, the fact that collagen VI producing cells in skeletal muscle are interstitial mesenchymal cells can support proof of concept for stem cell-based therapy.